JoVE Visualize What is visualize?
Stop Reading. Start Watching.
Advanced Search
Stop Reading. Start Watching.
Regular Search
Find video protocols related to scientific articles indexed in Pubmed.
PLA2G2A overexpression is associated with poor therapeutic response and inferior outcome in rectal cancer patients receiving neoadjuvant concurrent chemoradiotherapy.
Histopathology
PUBLISHED: 11-14-2014
Show Abstract
Hide Abstract
The aim of this study was to investigate the prognostic impact of PLA2G2A expression and its role in predicting the response to neoadjuvant concurrent cheomoradiotherapy (CCRT) in rectal cancer.
Related JoVE Video
Nosocomial neonatal legionellosis associated with water in infant formula, taiwan.
Emerging Infect. Dis.
PUBLISHED: 10-24-2014
Show Abstract
Hide Abstract
We report 2 cases of neonatal Legionella infection associated with aspiration of contaminated water used in hospitals to make infant formula. The molecular profiles of Legionella strains isolated from samples from the infants and from water dispensers were indistinguishable. Our report highlights the need to consider nosocomial legionellosis among neonates who have respiratory symptoms.
Related JoVE Video
Fibroblast growth factor receptor 2 overexpression is predictive of poor prognosis in rectal cancer patients receiving neoadjuvant chemoradiotherapy.
J. Clin. Pathol.
PUBLISHED: 09-30-2014
Show Abstract
Hide Abstract
Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is an increasingly used therapeutic strategy for advanced rectal cancer, but risk stratification and final outcomes remain suboptimal. Recently, the oncogenic role of the fibroblast growth factor/fibroblast growth factor receptor (FGFR) signalling pathway has been recognised; however, its clinical significance in rectal cancer has not been elucidated. In this study, we identify and validate targetable drivers associated with the FGFR signalling pathway in rectal cancer patients treated with CCRT.
Related JoVE Video
Pediatric Invasive Pneumococcal Disease in Taiwan Following a National Catch-Up Program with the 13-Valent Pneumococcal Conjugate Vaccine.
Pediatr. Infect. Dis. J.
PUBLISHED: 09-24-2014
Show Abstract
Hide Abstract
Seven-valent pneumococcal conjugate vaccine (PCV) has been available in Taiwan since late 2005. A national catch-up program was launched in Taiwan in 2013, providing one dose of 13-valent PCV to children aged 2-5 years. Here, we report the epidemiology of invasive pneumococcal disease (IPD) in children aged ?5 years in this setting.
Related JoVE Video
Overexpression of REG4 confers an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy.
J Surg Oncol
PUBLISHED: 08-22-2014
Show Abstract
Hide Abstract
Neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery is the standard treatment for locally advanced rectal cancer. Through data mining from published transcriptomic database, we identified Regenerating Gene Type IV (REG4) as the most significantly associated gene with resistance to CCRT. This study examined the prognostic impact of REG4 expression in patients with rectal cancer receiving neoadjuvant CCRT.
Related JoVE Video
Work stress and subsequent risk of internet addiction among information technology engineers in Taiwan.
Cyberpsychol Behav Soc Netw
PUBLISHED: 06-20-2014
Show Abstract
Hide Abstract
Work stress, as defined by the Demand-Control-Support (DCS) model and the Effort-Reward Imbalance (ERI) model, has been found to predict risks for depression, anxiety, and substance addictions, but little research is available on work stress and Internet addiction. The aims of this study are to assess whether the DCS and ERI models predict subsequent risks of Internet addiction, and to examine whether these associations might be mediated by depression and anxiety. A longitudinal study was conducted in a sample (N=2,550) of 21-55 year old information technology engineers without Internet addiction. Data collection included questionnaires covering work stress, demographic factors, psychosocial factors, substance addictions, Internet-related factors, depression and anxiety at wave 1, and the Internet Addiction Test (IAT) at wave 2. Ordinal logistic regression was used to assess the associations between work stress and IAT; path analysis was adopted to evaluate potentially mediating roles of depression and anxiety. After 6.2 months of follow-up, 14.0% of subjects became problematic Internet users (IAT 40-69) and 4.1% pathological Internet users (IAT 70-100). Job strain was associated with an increased risk of Internet addiction (odds ratio [OR] of having a higher IAT outcome vs. a lower outcome was 1.53); high work social support reduced the risk of Internet addiction (OR=0.62). High ER ratio (OR=1.61) and high overcommitment (OR=1.68) were associated with increased risks of Internet addiction. Work stress defined by the DCS and ERI models predicted subsequent risks of Internet addiction.
Related JoVE Video
Overexpression of CPS1 is an independent negative prognosticator in rectal cancers receiving concurrent chemoradiotherapy.
Tumour Biol.
PUBLISHED: 05-26-2014
Show Abstract
Hide Abstract
Locally advanced rectal cancers are currently treated with neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery, but stratification of risk and final outcomes remain suboptimal. In view of the fact that glutamine metabolism is usually altered in cancer, we profiled and validated the significance of genes involved in this pathway in rectal cancers treated with CCRT. From a published transcriptome of rectal cancers (GSE35452), we focused on glutamine metabolic process-related genes (GO:0006541) and found upregulation of carbamoyl phosphate synthetase 1 (CPS1) gene most significantly predicted poor response to CCRT. We evaluated the expression levels of CPS1 using immunohistochemistry to analyze tumor specimens obtained during colonoscopy from 172 rectal cancer patients. Expression levels of CPS1 were further correlated with major clinicopathological features and survivals in this validation cohort. To further confirm CPS1 expression levels, Western blotting was performed for human colon epithelial primary cell (HCoEpiC) and four human colon cancer cells, including HT29, SW480, LoVo, and SW620. CPS1 overexpression was significantly related to advanced posttreatment tumor (T3, T4; P?=?0.006) and nodal status (N1, N2; P?
Related JoVE Video
Paxillin promotes tumor progression and predicts survival and relapse in oral cavity squamous cell carcinoma by microRNA-218 targeting.
Carcinogenesis
PUBLISHED: 04-29-2014
Show Abstract
Hide Abstract
High-risk human papillomavirus (HPV) 16-infected oral cavity squamous cell carcinoma (OCSCC) differs significantly from non-HPV-infected OCSCC. However, the molecular pathogenesis of HPV-infected OCSCC remains unclear. Paxillin (PXN) has been reported to promote lung tumor progression by miR-218 targeting. In addition, expression of miR-218 has been shown to be reduced by HPV16 E6 in cervical cancer. We thus asked whether PXN can promote tumor progression by E6-reduced miR-218 in OCSCC, especially in HPV-infected OCSCC. Mechanistic studies demonstrated that PXN expression increased markedly upon E6-mediated reductions in miR-218, resulting in increased colony formation and invasion capabilities in HPV-infected OCSCC cells. Among tumor specimens, HPV16/18 infection was negatively associated with miR-218 expression and positively associated with PXN expression. Kaplan-Meier and Cox regression models demonstrated that patients with low-miR-218 tumors or high-PXN tumors exhibited shorter overall survival (OS) and relapse-free survival (RFS) than those with high-miR-218 tumors or low-PXN tumors. Interestingly, HPV-infected patients with low-miR-218, high-PXN tumors and both combinations exhibited the worst OS and RFS compared with patients in their counterparts. These observations in patients were consistent with the findings from the cell model. Therefore, we suggest that PXN might be targeted to suppress tumor progression and consequently to improve outcomes in OCSCC, especially in HPV-infected OCSCC.
Related JoVE Video
AMACR overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma.
Tumour Biol.
PUBLISHED: 04-22-2014
Show Abstract
Hide Abstract
The molecular prognostic adjunct in patients with nasopharyngeal carcinomas (NPCs) still remains obscured. Through data mining from published transcriptomic database, alpha-methylacyl-CoA racemase (AMACR) was first identified as a differentially upregulated gene in NPC tissues, which is a key enzyme for isometric conversion of fatty acids entering the ?-oxidation. Given the roles of AMACR in prognostication and frontline therapeutic regimen of common carcinomas, such as prostate cancer, we explored AMACR immunoexpression status and its clinical significance in NPC patients. AMACR immunohistochemistry was retrospectively performed and analyzed using H-score for biopsy specimens from 124 NPC patients who received standard treatment without distant metastasis at initial diagnosis. Those cases with H-score larger than the median value were construed as featuring AMACR overexpression. The findings were correlated with the clinicopathological variables, disease-specific survival (DSS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS). Endogenous AMACR protein expressions were assessed by real-time reverse-transcription polymerase chain reaction (RT-PCR) and Western blotting in NPC cells and non-neoplastic mucosal cells. AMACR overexpression was significantly associated with increment of primary tumor status (P?=?0.009) and univariately predictive of adverse outcomes for DSS, DMFS, and LRFS. In the multivariate comparison, AMACR overexpression still remained prognostically independent to portend worse DSS (P?=?0.006, hazard ratio?=?2.129), DMFS (P?=?0.001, hazard ratio?=?2.795), and LRFS (P?=?0.041, hazard ratio?=?2.009), together with advanced American Joint of Cancer Committee (AJCC) stages III-IV. Compared with non-neoplastic cells, both HONE1 and TW01 NPC cells demonstrated markedly increased AMACR expression. AMACR overexpression was identified as an important prognosticator and a potential therapeutic target in the future.
Related JoVE Video
Overexpression of ANXA1 confers independent negative prognostic impact in rectal cancers receiving concurrent chemoradiotherapy.
Tumour Biol.
PUBLISHED: 03-26-2014
Show Abstract
Hide Abstract
Neoadjuvant concurrent chemoradiation therapy (CCRT) is an increasingly common therapeutic strategy for rectal cancer. Clinically, it remains a major challenge to predict therapeutic response and patient outcomes after CCRT. Annexin I (ANXA1), encoded by ANXA1, is a Ca(2+)/phospholipid-binding protein that mediates actin dynamics and cellular proliferation, as well as suggesting tumor aggressiveness and predicting therapeutic response in certain malignancies. However, expression of ANXA1 has never been reported in rectal cancer receiving CCRT. This study examined the predictive and prognostic impact of ANXA1 expression in patients with rectal cancer following neoadjuvant CCRT. We identified ANXA1 as associated with resistance to CCRT through data mining from a published transcriptomic dataset. Its immunoexpression was retrospectively assessed using H scores on pre-treatment biopsies from 172 rectal cancer patients treated with neoadjuvant CCRT followed by curative surgery. Results were correlated with clinicopathological features, therapeutic response, tumor regression grade (TRG), and metastasis-free survival (MeFS), as well as local recurrent-free survival (LRFS) and disease-specific survival (DSS). High expression of ANXA1 was associated with advanced pre-treatment tumor status (T3, T4, p?=?0.022), advanced pre-treatment nodal status (N1, N2, p?=?0.004), advanced post-treatment tumor status (T3, T4, p?
Related JoVE Video
Cyclin-dependent kinase 4 overexpression is mostly independent of gene amplification and constitutes an independent prognosticator for nasopharyngeal carcinoma.
Tumour Biol.
PUBLISHED: 02-22-2014
Show Abstract
Hide Abstract
Data mining in the public domain demonstrates that cyclin-dependent kinase 4 (CDK4) is highly expressed in nasopharyngeal carcinomas (NPC). Associated with cyclin-D, CDK4 phosphorylates and inactivates retinoblastoma (Rb) protein family members and mediates progression through the G1- to the S-phase of the cell cycle. Amplification and overexpression of CDK4 has been identified in various human malignancies. However, its expression and amplification has never been systemically evaluated in NPC. This study aimed to evaluate the amplification and expression status, correlation with clinicopathological features, and prognostic implications of CDK4 based on public domain dataset and in our well-defined cohort of NPC patients. The association between CDK4 transcript level and gene dosage was explored by analysis of an independent public domain dataset. We retrospectively assessed CDK4 immunoexpression in biopsies of 124 consecutive NPC patients devoid of initial distant metastasis and treated according to consistent guidelines. The results were correlated with clinicopathological features, local recurrence-free survival (LRFS), distant metastasis-free survival (DMeFS), and disease-specific survival (DSS). High levels of CDK4 protein were positively correlated with the T 3, 4 status (p = 0.024); N 2, 3 status (p < 0.001); and the American Joint Committee on Cancer stage 3, 4 (p < 0.001). Multivariate analysis suggested high CDK4 expression was an independent prognostic indicator of worse DMeFS (p = 0.001, hazard ratio (HR)?= 3.226) and DSS (p = 0.037, HR = 1.838). Although CDK4 is frequently upregulated, its gene locus is very uncommonly amplified in NPC. CDK4 overexpression is mostly independent with gene amplification and represents a potential prognostic biomarker in NPC and may indicate tumor aggressiveness through cell cycle dysregulation.
Related JoVE Video
Deficiency in asparagine synthetase expression in rectal cancers receiving concurrent chemoradiotherapy: negative prognostic impact and therapeutic relevance.
Tumour Biol.
PUBLISHED: 02-19-2014
Show Abstract
Hide Abstract
Locally advanced rectal cancers are currently treated with neoadjuvant concurrent chemoradiotherapy (CCRT) followed by surgery, but risk stratification and final outcomes remain suboptimal. In this study, we identify and validate targetable metabolic drivers relevant to the prognosis of patients with rectal cancer treated with CCRT. Using a published transcriptome of rectal cancers, we found that asparagine synthetase (ASNS) gene significantly predicted the response to CCRT. From 172 patients with rectal cancer, the expression levels of ASNS, using immunohistochemistry assays, were further evaluated in tumor specimens initially obtained by using colonoscopy. Expression levels of ASNS were further correlated with major clinicopathological features and clinical survivals in this valid cohort. ASNS deficiency was significantly related to advanced posttreatment tumor (T3, T4; P = .015) and nodal status (N1, N2; P = .004) and inferior tumor regression grade (P < .001). In survival analyses, ASNS deficiency was significantly associated with shorter local recurrence-free survival (LRFS; P = .0039), metastasis-free survival (MeFS; P = .0001), and disease-specific survival (DSS; P = .0006). Furthermore, ASNS deficiency was independently predictive of worse outcomes for MeFS (P = .012, hazard ratio = 3.691) and DSS (P = .022, hazard ratio = 2.845), using multivariate analysis. ASNS deficiency is correlated with poor therapeutic response and worse survivals in patients with rectal cancer receiving neoadjuvant CCRT. These findings indicate that ASNS is a prognostic factor with therapeutic potential for treating rectal cancer.
Related JoVE Video
DSSylation, a novel protein modification targets proteins induced by oxidative stress, and facilitates their degradation in cells.
Protein Cell
PUBLISHED: 02-11-2014
Show Abstract
Hide Abstract
Timely removal of oxidatively damaged proteins is critical for cells exposed to oxidative stresses; however, cellular mechanism for clearing oxidized proteins is not clear. Our study reveals a novel type of protein modification that may play a role in targeting oxidized proteins and remove them. In this process, DSS1 (deleted in split hand/split foot 1), an evolutionally conserved small protein, is conjugated to proteins induced by oxidative stresses in vitro and in vivo, implying oxidized proteins are DSS1 clients. A subsequent ubiquitination targeting DSS1-protein adducts has been observed, suggesting the client proteins are degraded through the ubiquitin-proteasome pathway. The DSS1 attachment to its clients is evidenced to be an enzymatic process modulated by an unidentified ATPase. We name this novel protein modification as DSSylation, in which DSS1 plays as a modifier, whose attachment may render target proteins a signature leading to their subsequent ubiquitination, thereby recruits proteasome to degrade them.
Related JoVE Video
A pulsatile mass in the retropharynx: dangerous aberrations of the cervical carotid artery.
J Craniofac Surg
PUBLISHED: 01-29-2014
Show Abstract
Hide Abstract
Aberrations of the cervical internal carotid artery can be detected in the nasopharynx, oropharynx, and hypopharynx. Most previous literature reviews have focused on an analysis of the anatomic variations. However, clinical symptoms and physical examination findings have been rarely reported. Our clinical study describes a 63-year-old woman who presented with a lumpy and sore throat. We found an obvious protruding pulsatile mass in her retropharynx. Furthermore, an additional head and neck computed tomographic scan showed a variant course of the left common carotid artery and left internal carotid artery in the retropharynx and oropharynx.
Related JoVE Video
The safety and immunogenicity of a MF59-adjuvanted H5N1 prepandemic influenza vaccine in healthy adults primed with homologous or heterologous H5N1 vaccines: an observational study.
BMC Infect. Dis.
PUBLISHED: 01-09-2014
Show Abstract
Hide Abstract
BackgroundWorld Health Organization (WHO) has recommended individuals with increased risk of contracting influenza A H5N1 infection to be immunized against the virus during the inter-pandemic period. Safety and immunogenicity of H5N1 vaccine among participants primed with homologous or heterologous H5N1 vaccines produced by diverse manufactures have not been reported.MethodsHealthy individuals aged 20 to 60 years old were recruited and stratified into three groups: participants without priming (control group), participants primed with A/Indonesia/05/2005 vaccine, participants primed with A/Vietnam/1194/2004 vaccine and A/Indonesia/05/2005 vaccine. Enrolled participants received two doses of MF59-adjuvanted A/Vietnam/1194/2004 vaccine (study vaccine). Solicited reactions were recorded by vaccine recipients. Blood samples were obtained for hemagglutination inhibition test.ResultsA total of 131 participants were enrolled. No significant adverse events were recorded. Tenderness, fatigue and general muscle ache were the most common solicited reactions which alleviated within one week of immunization. Three weeks after two doses of the study vaccine, 63%, 68% and 88% were in seroprotective status in the control group, A/Indonesia/05/2005 primed group and A/Vietnam/1194/2004 and A/Indonesia/05/2005 primed group, respectively. Participants primed with A/Vietnam/1194/2004 and A/Indonesia/05/2005 showed high immune response after booster with one dose of the study vaccine.ConclusionThe study vaccine did not cause severe adverse events. It elicited mostly mild to moderate reactions among participants. Participants primed with A/Vietnam/1194/2004 and A/Indonesia/05/2005 vaccine showed higher immune response than those without priming or primed with A/Indonesia/05/2005 vaccine. The report suggested those with an increased risk of influenza A H5N1 virus exposure may benefit from receiving influenza A H5N1 priming during the inter-pandemic period if the antigenicity of the pandemic influenza strain is similar to that of the priming strain.
Related JoVE Video
Diabetes and risk of tuberculosis relapse: nationwide nested case-control study.
PLoS ONE
PUBLISHED: 01-01-2014
Show Abstract
Hide Abstract
The aim of this study was to investigate the association between diabetes mellitus (DM) and tuberculosis (TB) relapse using the nationwide TB registry in Taiwan. We conducted a case-control study nested within a nationwide cohort of all incident cases of pulmonary TB that were notified during 2006-2007 and had completed anti-TB treatment. The relapse of TB was confirmed by bacteriological or pathological findings. For each relapse case, one control was selected from the study cohort matching by time since treatment completion. DM status was ascertained by medical chart review and cross-matching with the National Health Insurance claims database. A total of 305 cases of relapse were identified after a median follow-up of 3 years (relapse rate: 488 per 100,000 person-year; 95% confidence interval (CI): 434-546). Presence of DM during previous anti-TB treatment was 34.0% and 22.7% in cases and controls, respectively. After adjusting for other potential confounders, DM was associated with increased risk of TB relapse (adjusted odds ratio: 1.96, 95% CI: 1.22-3.15). Only one-third of the DM-TB patients in our study received glycaemic monitoring using HbA1c during anti-TB treatment. Presence of DM was independently associated with risk of TB relapse. TB programs should seriously consider rigorous glucose control in DM-TB patients.
Related JoVE Video
A Large Outbreak of Salmonellosis Associated with Sandwiches Contaminated with Multiple Bacterial Pathogens Purchased via an Online Shopping Service.
Foodborne Pathog. Dis.
PUBLISHED: 12-06-2013
Show Abstract
Hide Abstract
Abstract Food sold over the internet is an emerging business that also presents a concern with regard to food safety. A nationwide foodborne disease outbreak associated with sandwiches purchased from an online shop in July 2010 is reported. Consumers were telephone interviewed with a structured questionnaire and specimens were collected for etiological examination. A total of 886 consumers were successfully contacted and completed the questionnaires; 36.6% had become ill, with a median incubation period of 18?h (range, 6-66?h). The major symptoms included diarrhea (89.2%), abdominal pain (69.8%), fever (47.5%), headache (32.7%), and vomiting (17.3%). Microbiological laboratories isolated Salmonella enterica serovar Enteritidis, Salmonella Virchow, Staphylococcus aureus, Bacillus cereus, and enterotoxigenic Escherichia coli from the contaminated sandwiches, Salmonella Enteritidis and Salmonella Virchow from the patients, and Salmonella Enteritidis and Staphylococcus aureus from food handlers. Pulsed-field gel electrophoresis genotyping suggested a common origin of Salmonella bacteria recovered from the patients, food, and a food handler. Among the pathogens detected, the symptoms and incubation period indicated that Salmonella, likely of egg origin, was the probable causative agent of the outbreak. This outbreak illustrates the importance of meticulous hygiene practices during food preparation and temperature control during food shipment and the food safety challenges posed by online food-shopping services.
Related JoVE Video
Resveratrol and P-glycoprotein Inhibitors Enhance the Anti-Skin Cancer Effects of Ursolic Acid.
Mol. Cancer Res.
PUBLISHED: 09-26-2013
Show Abstract
Hide Abstract
Ursolic acid, present in apples, rosemary, and other sources, is known to inhibit tumor formation and tumor cell viability in multiple systems, including skin. However, various cancers are resistant to ursolic acid treatment. Herein, skin carcinoma cells (Ca3/7) as compared with skin papilloma cells (MT1/2) displayed more resistance to ursolic acid-induced cytotoxicity. Interestingly, Ca3/7 cells had elevated levels of P-glycoprotein (P-gp), an ATP-dependent efflux pump that mediates resistance to chemotherapy in preclinical and clinical settings, and not only accumulated less but also more rapidly expelled the P-gp substrate rhodamine 123 (Rh123) indicating ursolic acid is transported by P-gp. To determine whether P-gp inhibition can enhance ursolic acid-mediated cytotoxicity, cells were challenged with P-gp inhibitors verapamil or cyclosporin A. Alternatively, cells were pretreated with the natural compound resveratrol, a known chemotherapy sensitizer. Verapamil and resveratrol enhanced the effects of ursolic acid in both cell lines, whereas cyclosporin A only did so in Ca3/7 cells. Similarly, verapamil inhibited Rh123 efflux in both lines, whereas cyclosporin A only inhibited Rh123 efflux in Ca3/7 cells. Resveratrol did not inhibit Rh123 efflux in either line, indicating the synergistic effects of resveratrol and ursolic acid are not manifest by inhibition of P-gp-mediated efflux of ursolic acid. These results indicate that the anti-skin cancer effects of ursolic acid are enhanced with P-gp inhibitors. In addition, resveratrol and ursolic acid interact synergistically, but not through inhibition of P-gp. Implications: Resveratrol and/or p-glycoprotein inhibitors in combination with ursolic acid are an effective anti-skin cancer regimen. Mol Cancer Res; 11(12); 1521-9. ©2013 AACR.
Related JoVE Video
Overexpression of stathmin 1 confers an independent prognostic indicator in nasopharyngeal carcinoma.
Tumour Biol.
PUBLISHED: 08-17-2013
Show Abstract
Hide Abstract
Data mining on public domain identified that stathmin 1 (STMN1) transcript was significantly higher expressed in nasopharyngeal carcinoma (NPC). Also known as the oncoprotein 18, STMN1 performs an important function in regulating rapid microtubule remodeling of the cytoskeleton in response to the cellular conditions. Immunoexpression of STMN1 was retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The outcome was correlated with clinicopathological features and patient survivals. Results indicated that high STMN1 expressions (50 %) were correlated with advanced age (p?=?0.027), higher T stage (p?=?0.003), and overall clinical stage (p?=?0.006) by the 7th American Joint Committee of Cancer Staging. In multivariate analyses, high STMN1 expression emerged as an independent prognosticator for worse disease-specific survival (p?=?0.001), distal metastasis-free survival (p?=?0.003), and local recurrence-free survival (p?=?0.006). Exogenous expression of E2F transcription factor 1 (E2F1) or/and its dimeric partner, transcription factor Dp-1 (TFDP1), notably induced the STMN1 protein level in a NPC-derived cell line, TW01. Accordingly, high STMN1 protein level is commonly associated with adverse prognosticators and confers tumor aggressiveness in patients with NPC, and its upregulation might be attributed to E2F1 and/or TFDP1 transactivation.
Related JoVE Video
Fibronectin overexpression is associated with latent membrane protein 1 expression and has independent prognostic value for nasopharyngeal carcinoma.
Tumour Biol.
PUBLISHED: 08-12-2013
Show Abstract
Hide Abstract
Despite recent improvements in the diagnosis and treatment, the final outcomes in patients with nasopharyngeal carcinomas (NPC) still remain suboptimal. Through data mining from published transcriptomic database with further bioinformatic validation, fibronectin (FN1) was identified as a differentially upregulated gene in NPC tissues, which implicates the transition from epithelial to mesenchymal phenotype (EMT) and promotes metastasis. Given the roles of fibronectin in risk stratification and in the frontline therapeutics of common carcinomas, such as renal cell cancer, we explored fibronectin immunoexpression status and its associations with clinicopathological variables and survival in a well-defined cohort of NPC patients. Fibronectin immunohistochemistry was retrospectively performed and analyzed using H-score for 124 biopsy specimens from NPC patients who received standard treatment without distant metastasis at initial diagnosis. Those cases with H-score higher than the median value were regarded as fibronectin overexpression. The findings were correlated with clinicopathological variables, EBV latent membrane protein 1 (LMP1) expression, disease-specific survival (DSS), distant metastasis-free survival (DMFS), and local recurrence-free survival (LRFS). Fibronectin overexpression was significantly associated with American Joint Committee on Cancer (AJCC) stages III-IV (p?=?0.019) and LMP1 expression (p?=?0.004), and univariately predictive of adverse outcomes for DSS, DMFS, and LRFS (all p?
Related JoVE Video
Legionnaires disease caused by Legionella longbeachae in Taiwan, 2006-2010.
Int. J. Infect. Dis.
PUBLISHED: 08-06-2013
Show Abstract
Hide Abstract
The aim of the present study was to investigate the epidemiology of Legionnaires disease (LD) caused by Legionella longbeachae in Taiwan during 2006-2010. A total of six cases were identified prospectively, accounting for 1.6% of all laboratory-confirmed LD cases and 4.4% of culture-positive LD cases. All six cases occurred between April and August. The male to female ratio was 0.5. These six LD patients had a higher median age than those with LD due to Legionella pneumophila. Four of the six patients presented with pleural effusion and five survived the infection episode. Only two patients had a potential soil contact history prior to LD onset. The patients resided in divergent geographical areas without a common exposure history. The individual genomic DNA banding patterns of the six L. longbeachae isolates analyzed by pulsed-field gel electrophoresis (PFGE) were unique, supporting the hypothesis that the L. longbeachae infections occurred sporadically.
Related JoVE Video
A web-based audiometry database system.
J. Formos. Med. Assoc.
PUBLISHED: 07-23-2013
Show Abstract
Hide Abstract
To establish a real-time, web-based, customized audiometry database system, we worked in cooperation with the departments of medical records, information technology, and otorhinolaryngology at our hospital. This system includes an audiometry data entry system, retrieval and display system, patient information incorporation system, audiometry data transmission program, and audiometry data integration. Compared with commercial audiometry systems and traditional hand-drawn audiometry data, this web-based system saves time and money and is convenient for statistics research.
Related JoVE Video
The role of interleukin-10 in the progression of human papillomavirus-associated lung carcinoma.
Oncoimmunology
PUBLISHED: 07-17-2013
Show Abstract
Hide Abstract
The secretion of interleukin-10 by both malignant and immune cells promotes the progression of lung tumors, hence negatively impacting on patient prognosis. As interleukin-10 mediates oncogenic effects through the PI3K/AKT signaling pathway, PI3K/AKT inhibitors might sensitize cancer cells to chemotherapy, thus favoring tumor regression and improving disease outcome.
Related JoVE Video
TOP2A overexpression as a poor prognostic factor in patients with nasopharyngeal carcinoma.
Tumour Biol.
PUBLISHED: 06-24-2013
Show Abstract
Hide Abstract
Despite the advances in diagnostic imaging and treatment modalities, the risk stratification and final outcomes in patients with nasopharyngeal carcinomas (NPC) still remain suboptimal. Through data mining from published transcriptomic database, topoisomerase II? (TOP2A) was first identified as a differentially upregulated gene in NPC tissues, which implicates cell division via selective cleavage, rearrangement, and re-ligation of DNA strands. Given the roles of TOP2A in prognostication and in the frontline therapeutic regimen of common carcinomas, such as breast cancer, we explored TOP2A immunoexpression status and its associations with clinicopathological variables and survival in a well-defined cohort of NPC patients. TOP2A immunohistochemistry was retrospectively performed and analyzed using H-score method for biopsy specimens from 124 NPC patients who received standard treatment without distant metastasis at initial diagnosis. Those cases with H-score larger than the median value were construed as featuring TOP2A overexpression. The findings were correlated with the clinicopathological variables, disease-specific survival (DSS) and distant metastasis-free survival (DMFS). TOP2A overexpression was significantly associated with American Joint of Cancer Committee (AJCC) stages III-IV (p?=?0.019) and univariately predictive of adverse outcomes for DSS (p?=?0.0078) and DMFS (p?=?0.0003). In the multivariate comparison, TOP2A overexpression remained prognostically independent to portend worse DSS (p?=?0.047, hazard ratio?=?1.732) and DMFS (p?=?0.003, hazard ratio?=?2.569), together with advanced AJCC stages III-IV. TOP2A expression is upregulated in a subset of NPCs and its increased immunoexpression significantly correlated with advanced stages and tumor aggressiveness, justifying the potentiality of TOP2A as a prognostic biomarker and a novel therapeutic target of NPC.
Related JoVE Video
Political and economic characteristics as moderators of the relationship between health services and infant mortality in less-developed countries.
J Epidemiol Community Health
PUBLISHED: 06-17-2013
Show Abstract
Hide Abstract
Few studies have addressed how political and economic contexts shape the effects of health services and environment, such that a politically and economically unstable society, despite having sufficient health professionals and facilities, finds it difficult to transfer health resources into actual population health performance. We examined whether political and economic characteristics moderate the effects of health services on infant mortality rates (IMR) in less-developed countries.
Related JoVE Video
Deficiency in expression and epigenetic DNA Methylation of ASS1 gene in nasopharyngeal carcinoma: negative prognostic impact and therapeutic relevance.
Tumour Biol.
PUBLISHED: 06-13-2013
Show Abstract
Hide Abstract
The risk stratification and final outcomes in patients with nasopharyngeal carcinomas (NPC) still remain suboptimal. Our principal goals were to identify and validate targetable metabolic drivers relevant to pathogenesis of NPC using a published transcriptome. One prominently downregulated gene regulating amino acid metabolism was found to be argininosuccinate synthetase (ASS1). Attributable to epigenetic DNA methylation, ASS1 deficiency may link to the therapeutic sensitivity to the arginine-depriving agents and promote tumor aggressiveness through its newly identified tumor suppressor function. ASS1 immunohistochemistry was therefore examined in a well-defined cohort of 124 NPC biopsy specimens and in the neck lymph node metastases of another ten independent cases. For the latter, bisulphite pyrosequencing was performed to evaluate the extent of ASS1 gene methylation. ASS1 protein deficiency was identified in 64 of 124 cases (51.6 %), significantly related to T3-T4 status (p?=?0.006), and univariately associated with inferior local recurrence-free survival (p?=?0.0427), distant metastasis-free survival (DMFS; p?=?0.0036), and disease-specific survival (DSS; p?=?0.0069). Together with advanced AJCC stages III-IV, ASS1 protein deficiency was also independently predictive of worse outcomes for the DFMS (p?=?0.010, hazard ratio?=?2.241) and DSS (p?=?0.020, hazard ratio?=?1.900). ASS1 promoter hypermethylation was detected in eight of ten neck nodal metastatic lesions by bisulphite pyrosequencing and associated with ASS1 protein deficiency (p?
Related JoVE Video
Different impact of IL10 haplotype on prognosis in lung squamous cell carcinoma and adenocarcinoma.
Anticancer Res.
PUBLISHED: 06-11-2013
Show Abstract
Hide Abstract
Polymorphisms (1082A>G, - 819C>T, and -592G>A) in the interleukin-10 (IL10) promoter are associated with its transcriptional activity. IL10 induction by cigarette smoking plays a role in smoking-related lung tumor progression. We therefore expected to find a difference in impact of IL10 haplotypes on overall survival (OS) and relapse-free survival (RFS) between squamous cell carcinomas (SCC) and adenocarcinomas (ADC) of lung.
Related JoVE Video
Nicotinamide N-methyltransferase overexpression is associated with Akt phosphorylation and indicates worse prognosis in patients with nasopharyngeal carcinoma.
Tumour Biol.
PUBLISHED: 06-06-2013
Show Abstract
Hide Abstract
Nicotinamide N-methyltransferase (NNMT) is overexpressed in many human cancers and is associated with poor prognosis. Akt (also known as protein kinase B) is an evolutionarily conserved serine/threonine kinase, serving as a downstream effector of the phosphatidylinositol 3-kinase signaling pathway. NNMT was first identified as a differentially upregulated gene in nasopharyngeal cancer tissues through data mining from published transcriptomic databases. Since no prior study has attempted to evaluate the clinical significance of NNMT or phosphorylated Akt (pAkt) expression in nasopharyngeal cancer, this study explores their expression in a large cohort of patients with nasopharyngeal cancer. The study included 124 nasopharyngeal cancer patients who were free of distant metastasis at initial diagnosis. Pathological slides were reviewed and clinical findings collected. We evaluated the expression of NNMT and pAkt immunohistochemically, stratified them into two groups (high and low expression) and examined the correlation with disease-specific survival (DSS), metastasis-free survival (MeFS), local recurrence-free survival (LRFS), and various clinicopathological factors. NNMT expression was significantly positively associated with pAkt expression. The high expression of both markers was significantly associated with an increment of tumor stage (p?=?0.006 and p?=?0.006, respectively). High expression of NNMT correlated significantly with a more aggressive clinical course and a significantly shorter DSS. Furthermore, NNMT expression and pAkt expression were strongly predictive of MeFS (p?=?0.008; p?=?0.0063) and LRFS (p?=?0.005; p?=?0.0125). In multivariate analysis, high expression of NNMT remained as a robust prognosticator for both end points evaluated. It independently portended inferior DSS (p?=?0.02, HR?=?1.976) and worse MeFS (p?=?0.029, HR?=?2.022) after tumor stage (p?=?0.033, HR?=?2.150; p?=?0.028, HR?=?2.942, for DSS and LRFS, respectively). We found NNMT positively correlated with pAkt expression and was independent adverse prognosticators of patient survival. NNMT therefore has potential utility as an indicator for prognosis, predicting treatment response to chemotherapy or radiation therapy, and even as a therapeutic target in the future.
Related JoVE Video
IL-10 promotes tumor aggressiveness via upregulation of CIP2A transcription in lung adenocarcinoma.
Clin. Cancer Res.
PUBLISHED: 06-06-2013
Show Abstract
Hide Abstract
Interleukin-10 (IL-10) determines virus persistent infection and promotes viral-associated tumor progression via tumor immune escape. However, the role of IL-10 in tumor progression and prognosis in lung adenocarcinoma remains controversial.
Related JoVE Video
Catastrophic venous air embolism during craniotomy in the supine position: the bleeding pattern as a warning sign?
J Craniofac Surg
PUBLISHED: 05-30-2013
Show Abstract
Hide Abstract
Venous air embolism is a serious complication during a neurosurgical procedure. Here is a case of a massive venous air embolism causing cardiac arrest in the supine position surgery. Identifying the alternative inflation and collapse of the sinus and taking emergency measures to avoid catastrophic result are important.
Related JoVE Video
A longitudinal ecological study of the influences of political, economic, and health services characteristics on under-five mortality in less-developed countries.
Health Place
PUBLISHED: 05-13-2013
Show Abstract
Hide Abstract
This study used a longitudinal dataset and lagged dependent-variable panel regression models to examine whether political and economic characteristics directly predict under-5-year mortality rates (U5MR), and moderate the effects of health services and environment on U5MR. We used a sample of 46 less-developed countries from 1980 to 2009. Our results showed that the effects of political and economic characteristics on U5MR varied by non-sub-Saharan and sub-Saharan countries. After controlling for baseline U5MR and other socioeconomic variables, while foreign investment and health services were negatively associated U5MR, democracy was positively associated with U5MR in nonsub-Saharan countries. In contrast, debt was positively associated with and democracy and foreign investment were negatively associated with U5MR in sub-Saharan countries. The interaction analyses indicated that for sub-Saharan countries, the effects of health services on U5MR only existed for countries with low foreign investment.
Related JoVE Video
Cerebrolysin enhances cognitive recovery of mild traumatic brain injury patients: double-blind, placebo-controlled, randomized study.
Br J Neurosurg
PUBLISHED: 05-08-2013
Show Abstract
Hide Abstract
Abstract In adults, mild traumatic brain injury (MTBI) frequently results in impairments of cognitive functions which would lead to psychological consequences in the future. Cerebrolysin is a nootropic drug, and can significantly improve cognitive function in patients with Alzheimers disease and stroke. The purpose of this study was to investigate how Cerebrolysin therapy enhances cognitive recovery for mild traumatic brain injury patients using a double-blinded, placebo-controlled, randomized phase II pilot study. Patients having head injury within 24 h sent to our hospital were screened and recruited if patients were alert and conscious, and had intracranial contusion haemorrhage. From July 2009 to June 2010, totally, thirty-two patients were recruited in the double-blinded, placebo-controlled, and randomized study. Patients were randomized to receive Cerebrolysin (Group A, once daily intravenous infusion of 30 mL Cerebrolysin over a 60-min period for 5 days) or placebo (Group B, same dosage and administration of normal saline as Group A). The primary outcome measures were differences of cognitive function including Mini-Mental Status Examination (MMSE), and Cognitive Abilities Screening Instrument (CASI) scores between baseline and week 1, between baseline and week 4, and between baseline and week 12. Thirty-two patients completed the trial. For Group A, the CASI score difference between baseline and week 12 was 21.0 ± 20.4, a significantly greater change than that of Group B (7.6 ± 12.1) (p = 0.0461). Besides, drawing function (one of the domains of CASI; p = 0.0066) on week 4 and both drawing function (p = 0.0472) and long-term memory (one of the domains of CASI; p = 0.0256) on week 12were also found to be significantly improved in the patients receiving Cerebrolysin treatment. Our results suggest that Cerebrolysin improves the cognitive function of the MTBI in patients at 3rd month after injury, especially for long-term memory and drawing function.
Related JoVE Video
Glutathione S-transferase mu2 suppresses cancer cell metastasis in non-small cell lung cancer.
Mol. Cancer Res.
PUBLISHED: 05-07-2013
Show Abstract
Hide Abstract
Glutathione S-transferase mu2 (GST-M2) is a phase II detoxification enzyme. Low expression of GST-M2 in lung cancers is due to hypermethylation of its promoter. Lung cancer with the GST mu-null genotype is associated with shorter survival. However, a correlation between GST-M2 and important clinical parameters, as well as the migration of GST-M2-defective cells in lung cancer, has not been established. In the present study, we investigate the role of GST-M2 in cell migration and actin disassembly in lung cancer cells. GST-M2 and CCN2 mRNA levels were significantly reduced in non-small cell lung cancer (NSCLC) tumors when compared with matched normal lung tissues in 82 patients with NSCLC. We found that high expressions of both GST-M2 and CCN2 are correlated with favorable survival of patients with lung cancer when compared with similar patients without GST-M2 or CCN2 expression. GST-M2 can induce CCN2 expression by driving the CCN2 proximal promoter. Overexpression of GST-M2 decreases the formation of filopodia, resulting in remodeling of the reorganized cytoskeletons. Overexpression of GST-M2 significantly suppressed cancer cell migration on wound-healing assay. In addition, overexpression of GST-M2 dramatically reduced tumor growth and metastasis in a xenograft mouse model. These data highlight the potential of GST-M2 as a novel tumor suppressor. GST-M2 increases the expression of CCN2 in lung cancer cells, which inhibits cancer cell migration in lung cancer and animal models.
Related JoVE Video
Clinicopathological significance of HuR expression in gallbladder carcinoma: with special emphasis on the implications of its nuclear and cytoplasmic expression.
Tumour Biol.
PUBLISHED: 04-21-2013
Show Abstract
Hide Abstract
Gallbladder carcinoma (GBC) is a relatively rare disease which pathogenesis is less clarified. Human antigen R (HuR), a RNA-binding protein, modulates the expressions of various cancer-related proteins by stabilizing or regulating the transcription of the corresponding messenger RNA. The significance of HuR expression in a large cohort with GBCs is yet to be evaluated. In total, 164 cases of GBC were selected, and immunostaining for HuR was performed. HuR nuclear (HuR-N) expression and HuR cytoplasmic (HuR-C) expression were evaluated by using a histochemical score. The results of HuR expression were correlated with various clinicopathological factors, disease-specific survival (DSS), and disease-free survival (DFS) in 161 patients with follow-up data. HuR-N overexpression was strongly associated with high histological grade (p = 0.001), vascular invasion (p < 0.001), and high Ki-67 labeling index (p < 0.001). HuR-C overexpression was significantly related to higher primary tumor status (p < 0.001), advanced tumor stage (p < 0.001), histological type (p = 0.006), high histological grade (p < 0.001), vascular and perineurial invasion (p < 0.001 and p = 0.002, respectively), tumor necrosis (p = 0.042), and high Ki-67 labeling index (p = 0.002). Besides, HuR-C overexpression also correlates with HuR-N overexpression (p < 0.001) and cyclin A overexpression (p = 0.026). HuR-N overexpression correlated with poor DFS (p = 0.0348) in univariate analysis, but HuR-C overexpression strongly correlated with a worse DSS and DFS in both univariate (both p < 0.0001) and multivariate (DSS, p = 0.006; DFS, p = 0.001) analyses. Subcellular localization of HuR expression correlates with different adverse phenotypes of GBC. Besides, HuR-C overexpression is an independent prognostic factor for dismal DSS and DFS, suggesting its roles in tumorigenesis or carcinogenesis and as a potential prognostic marker of GBC.
Related JoVE Video
Clitocybe nuda Activates Dendritic Cells and Acts as a DNA Vaccine Adjuvant.
Evid Based Complement Alternat Med
PUBLISHED: 03-08-2013
Show Abstract
Hide Abstract
This work represents the first evaluation of the effects of water extract of C. nuda (WE-CN), an edible mushroom, on murine bone marrow-derived dendritic cells (BMDCs) and the potential pathway through which the effects are mediated. Our experimental results show that WE-CN could induce phenotypic maturation of DCs, as shown by the increased expression of MHC and costimulatory molecules. In addition, it also induced the proinflammatory cytokines expression on DCs and enhanced both the proliferation and IFN- ? secretion of allogenic T cells. Therefore, since WE-CN did not induce maturation of DCs generated from mice with mutated TLR-4 or TLR-2, suggesting that TLR4 and TLR2 might function as membrane receptors for WE-CN. Moreover, the mechanism of action of WE-CN may be mediated by increased phosphorylation of ERK, p38, and JNK mitogen-activated protein kinase (MAPK) and increased NF- ? B p65 activity, which are important signaling molecules downstream of TLR-4 and TLR-2. Finally, coimmunization of mice with WE-CN and a HER-2/neu DNA vaccine induced a HER-2/neu-specific Th1 response that resulted in significant inhibition of HER-2/neu overexpressing mouse bladder tumor (MBT-2) growth. These data suggest that WE-CN induces DC maturation through TLR-4 and/or TLR-2 and that WE-CN can be used as an adjuvant in cancer vaccine immunotherapy.
Related JoVE Video
Differential Effects on Lung Cancer Cell Proliferation by Agonists of Glucocorticoid and PPAR? Receptors.
Mol. Carcinog.
PUBLISHED: 03-01-2013
Show Abstract
Hide Abstract
Glucocorticoids (GCs) are well-known anti-inflammatory compounds, but they also inhibit cell proliferation depending on cell type. Similarly, peroxisome proliferator-activated receptors (PPAR?, PPAR?, and PPAR?) also possess anti-proliferation properties beyond their canonical roles as metabolic mediators. In the present study, we investigated the potential additive or synergistic inhibitory effects on cancer cell proliferation by simultaneous application of fenofibrate and budesonide, agonists for PPAR? and glucocorticoid receptor, respectively. We observed differential effects on cell proliferation in A549 and SK-MES-1 lung cancer cells by budesonide and fenofibrate. Fenofibrate inhibited cell proliferation in both TP53 wild type and deficient lung cancer cells. The anti-proliferation effect of budesonide in TP53 wild type A549 cells was abolished in SK-MES-1 cells that do not have wild type TP53 protein. An additive effect against cell proliferation by budesonide and fenofibrate combination was observed only in TP53 wild type A549 cancer cells. Analysis of cell cycle distribution and cyclin profile indicated that the inhibition of cell proliferation was associated with G1 cell cycle arrest. The suppression of NF-?B activity and ERK signaling may contribute to the inhibition of cell proliferation by budesonide and or fenofibrate. The additive inhibitory effect on cell proliferation by budesonide and fenofibrate combination suggests that the same or greater therapeutic effect could be achieved with reduced dosage and side effects when the two compounds are applied simultaneously. © 2013 Wiley Periodicals, Inc.
Related JoVE Video
Molecular typing and epidemiology of Clostridium difficile in respiratory care wards of central Taiwan.
J Microbiol Immunol Infect
PUBLISHED: 02-27-2013
Show Abstract
Hide Abstract
BACKGROUND/PURPOSE: In industrialized countries, Clostridium difficile is the major cause of nosocomial diarrhea. This study involved a broad overview of baseline epidemiology for C. difficile in Taiwan. MATERIALS AND METHODS: Point prevalence was estimated from a prospective survey conducted in the respiratory care wards of six hospitals in central Taiwan. Polymerase chain reaction (PCR) ribotyping and multiple-locus variable-number tandem-repeat analysis (MLVA) were performed on all toxigenic C. difficile isolates, including asymptomatic and symptomatic strains. RESULTS: A total of 149 patients were screened for C. difficile; the point prevalence for C. difficile infection (CDI) and C. difficile colonization was 4% and 19%, respectively. CDI cases were significantly related to end-stage renal disease, and C. difficile colonization cases were significantly associated with previous admission to an acute-care facility. No hypervirulent PCR ribotype 027 strain was found. MLVA detected two clusters of CDI-related and three clusters of asymptomatic C. difficile strains circulating in wards. CONCLUSION: Our results demonstrate a high prevalence of toxigenic C. difficile colonization in hospitals. Infection control personnel should pay attention to the increasing numbers of CDI cases, and molecular typing for C. difficile should be performed when necessary.
Related JoVE Video
Overexpression of thymidylate synthetase confers an independent prognostic indicator in nasopharyngeal carcinoma.
Exp. Mol. Pathol.
PUBLISHED: 02-22-2013
Show Abstract
Hide Abstract
Data mining on public domain identified that thymidylate synthetase (TYMS) and dihydrofolate reductase (DHFR) transcripts were significantly higher expressed in nasopharyngeal carcinoma (NPC). In the folate pathway, TYMS catalyzes the methylation of deoxyuridylate to deoxythymidylate using 5,10-methylenetetrahydrofolate [5,10-CH2=THF, derived from tetrahydrofolate (THF)], as a cofactor. This function maintains the thymidine-5-prime monophosphate pool critical for DNA replication and repair and, THF is generated from dihydrofolate (DHF) through the activity of DHFR. Immunoexpression of TYMS and DHFR were retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The outcome was correlated with clinicopathological features and patient survivals. Results indicated that high TYMS (50%) expressions were correlated with primary tumor (p=0.008) and AJCC stage (p=0.006), and high DHFR (50%) expression were correlated with nodal status (p=0.039) and AJCC stage (p=0.029) (7th American Joint Committee on Cancer), respectively. In multivariate analyses, high TYMS expression emerged as an independent prognosticator for worse disease-specific survival (p<0.001), distal metastasis-free survival (p=0.002) and local recurrence-free survival (p<0.001), along with AJCC stage. Therefore, TYMS expression is common and associated with adverse prognosticators and might confer tumor aggressiveness through dysregulation of the nucleotide biosynthetic process.
Related JoVE Video
SKP2 overexpression is associated with a poor prognosis of rectal cancer treated with chemoradiotherapy and represents a therapeutic target with high potential.
Tumour Biol.
PUBLISHED: 01-03-2013
Show Abstract
Hide Abstract
The S-phase kinase-associated protein 2 (SKP2) oncoprotein is an E3 ubiquitin ligase. Overexpression of SKP2 was found in various human cancers, including colorectal cancers, but its potential role as a prognostic marker after neoadjuvant chemoradiotherapy (CRT) and for therapeutic intervention in rectal cancers is unknown. This study examined the correlation of SKP2 expression in the prognosis of rectal cancer patients and the viability of colorectal cancer cells treated with CRT. SKP2 immunoexpression was retrospectively assessed in pretreatment biopsies of 172 rectal cancer patients treated with neoadjuvant CRT followed by surgery. Results were correlated with clinicopathological features, therapeutic responses, and patient survival. Pharmacologic assays were used to evaluate the therapeutic relevance of Bortezomib in two colorectal cancer cell lines (HT-29 and SW480). High expression of SKP2 was correlated with the advanced Post-Tx nodal status (p = 0.002), Post-Tx International Union for Cancer Control stage (p = 0.002), and a lower-degree tumor regression grade (p < 0.001). Moreover, high expression of SKP2 (p = 0.027, hazard ratio 3.21) was an independent prognostic factor for local recurrence-free survival. In vitro, Bortezomib downregulated SKP2 expression, induced caspase activation, and decreased the viability of colorectal cancer cells with or without a combination with fluorouracil. Bortezomib also promoted caspase activation and gamma-H2AX formation in colorectal cancer cells concurrently treated with CRT. High expression of SKP2 was associated with a poor therapeutic response and adverse outcomes in rectal cancer patients treated with neoadjuvant CRT. In the presence of chemotherapy with or without radiotherapy, the promoted sensitivity of colorectal cancer cells to Bortezomib with an SKP2-repressing effect indicated that it is a potential therapeutic target.
Related JoVE Video
Number of nuclear divisions in the Drosophila blastoderm controlled by onset of zygotic transcription.
Curr. Biol.
PUBLISHED: 01-03-2013
Show Abstract
Hide Abstract
The cell number of the early Drosophila embryo is determined by exactly 13 rounds of synchronous nuclear divisions, allowing cellularization and formation of the embryonic epithelium. The pause in G2 in cycle 14 is controlled by multiple pathways, such as activation of DNA repair checkpoint, progression through S phase, and inhibitory phosphorylation of Cdk1, involving the genes grapes, mei41, and wee1. In addition, degradation of maternal RNAs and zygotic gene expression are involved. The zinc finger Vielfältig (Vfl) controls expression of many early zygotic genes, including the mitotic inhibitor frühstart. The functional relationship of these pathways and the mechanism for triggering the cell-cycle pause have remained unclear. Here, we show that a novel single-nucleotide mutation in the 3 UTR of the RNPII215 gene leads to a reduced number of nuclear divisions that is accompanied by premature transcription of early zygotic genes and cellularization. The reduced number of nuclear divisions in mutant embryos depends on the transcription factor Vfl and on zygotic gene expression, but not on grapes, the mitotic inhibitor Frühstart, and the nucleocytoplasmic ratio. We propose that activation of zygotic gene expression is the trigger that determines the timely and concerted cell-cycle pause and cellularization.
Related JoVE Video
Overexpression of CDC28 protein kinase regulatory subunit 1B confers an independent prognostic factor in nasopharyngeal carcinoma.
APMIS
PUBLISHED: 01-02-2013
Show Abstract
Hide Abstract
Data mining on public domain identified that CDC28 protein kinase regulatory subunit 1B (CKS1B) transcript was highly expressed in nasopharyngeal carcinoma (NPC). The expression of CKS1B protein and its clinicopathological associations in patients with NPC were further evaluated. Immunoexpression of CKS1B was retrospectively assessed in biopsies of 124 consecutive NPC patients without initial distant metastasis and treated with consistent guidelines. The correlations between CKS1B immunoexpression levels and clinicopathological features, as well as patient survivals, were analyzed. High CKS1B expression (49.2%) was correlated with the 7th American Joint Committee on Cancer (AJCC) stage (p = 0.014). In multivariate analyses, high CKS1B expression emerged as an independent prognostic factor for worse disease-specific survival (p < 0.001), metastasis-free survival (p < 0.001), and local recurrence-free survival (p = 0.001). High expression of CKS1B is common and associated with adverse prognostic factors and might confer tumor aggressiveness through dysregulation of the cyclin-dependent protein kinase (intrinsic regulatory activity) during cell cycle progression.
Related JoVE Video
Associations of Rsf-1 overexpression with poor therapeutic response and worse survival in patients with nasopharyngeal carcinoma.
J. Clin. Pathol.
PUBLISHED: 11-12-2011
Show Abstract
Hide Abstract
Deregulated chromatin remodelling often leads to aberrant gene expression in cells, thereby implicating tumour development and progression. As a subunit of remodelling and spacing factor complex, Rsf-1 (HBXAP), a novel nuclear protein with histone chaperon function, mediates ATPase-dependent chromatin remodelling and confers tumour aggressiveness in common carcinomas. However, the expression of Rsf-1 has never been reported in nasopharyngeal carcinoma (NPC). This study aimed at evaluating the expression status, associations with clincopathological variables and prognostic implications of Rsf-1 in a well-defined cohort of NPC.
Related JoVE Video
A hybrid nanostructure of platinum-nanoparticles/graphitic-nanofibers as a three-dimensional counter electrode in dye-sensitized solar cells.
Chem. Commun. (Camb.)
PUBLISHED: 09-26-2011
Show Abstract
Hide Abstract
We directly synthesized a platinum-nanoparticles/graphitic-nanofibers (PtNPs/GNFs) hybrid nanostructure on FTO glass. We applied this structure as a three-dimensional counter electrode in dye-sensitized solar cells (DSSCs), and investigated the cells photoconversion performance.
Related JoVE Video
An outbreak of coxsackievirus A6 hand, foot, and mouth disease associated with onychomadesis in Taiwan, 2010.
BMC Infect. Dis.
PUBLISHED: 08-14-2011
Show Abstract
Hide Abstract
In 2010, an outbreak of coxsackievirus A6 (CA6) hand, foot and mouth disease (HFMD) occurred in Taiwan and some patients presented with onychomadesis and desquamation following HFMD. Therefore, we performed an epidemiological and molecular investigation to elucidate the characteristics of this outbreak.
Related JoVE Video
A polymorphic -844T/C in FasL promoter predicts survival and relapse in non-small cell lung cancer.
Clin. Cancer Res.
PUBLISHED: 08-01-2011
Show Abstract
Hide Abstract
Fas ligand (FasL) -844T/C polymorphism (rs763110) has a demonstrated association with lung cancer risk. FasL -844CC with higher FasL expression has been suggested to contribute to tumor progression via immune escape. However, the impact of FasL -844T/C polymorphism on the clinical outcome of non-small cell lung cancer (NSCLC) remains to be identified.
Related JoVE Video
Anesthetic management of a repeat cesarean section in a parturient with severe peripartum cardiomyopathy requiring ECMO in a previous pregnancy: a case report.
Chang Gung Med J
PUBLISHED: 07-25-2011
Show Abstract
Hide Abstract
The number of pregnant women with cardiac disease is increasing with improvements in technology. In addition, more people are part of the national health insurance plan. However, there are few reports concerning the best method for anesthesia and mode of delivery in these high-risk patients. We report a 29-year-old woman scheduled for a planned caesarean section, who had a history of severe peripartum cardiomyopathy requiring extracorporeal membrane oxygenation in a previous pregnancy. The patient had regular prenatal care in our obstetric clinic. At 29 weeks gestation, she developed severe dyspnea. A chest radiograph revealed bilateral pulmonary edema and 2-dimensional echocardiography showed a global hypokinesis and severe valve regurgitation with left ventricular ejection fraction of 41.2%. She had an emergency caesarean section and a cardiovascular surgeon was consulted to stand-by. Anesthesia was induced by ketamine 25 mg, midazolam 2.5 mg and rocuronium 50 mg for rapid intubation. The patient tolerated the procedure well and was extubated on postoperative day 1. She was discharged one week after surgery. Postoperatively, the patient was followed in the obstetric and cardiovascular surgery outpatient departments and at 5 months after surgery she was in good condition without any complaints.
Related JoVE Video
CD34 Antigen: Determination of Specific Sites of Phosphorylation In Vitro and In Vivo.
Int J Mass Spectrom
PUBLISHED: 04-19-2011
Show Abstract
Hide Abstract
CD34, a type I transmembrane glycoprotein, is a surface antigen which is expressed on several cell types, including hematopoietic progenitors, endothelial cells, as well as mast cells. Recently, CD34 has been described as a marker for epidermal stem cells in mouse hair follicles, and is expressed in outer root sheath cells of the human hair follicle. Although the biological function and regulation of CD34 is not well understood, it is thought to be involved in cell adhesion as well as possibly having a role in signal transduction. In addition, CD34 was shown to be critical for skin tumor development in mice, although the exact mechanism remains unknown.Many proteins functions and biological activities are regulated through post-translational modifications. The extracellular domain of CD34 is heavily glycosylated but the role of these glycans in CD34 function is unknown. Additionally, two sites of tyrosine phosphorylation have been reported on human CD34 and it is known that CD34 is phosphorylated, at least in part, by protein kinase C; however, the precise location of the sites of phosphorylation has not been reported. In an effort to identify specific phosphorylation sites in CD34 and delineate the possible role of protein kinase C, we undertook the identification of the in vitro sites of phosphorylation on the intracellular domain of mouse CD34 (aa 309-382) following PKC treatment. For this work, we are using a combination of enzymatic proteolysis and peptide sequencing by mass spectrometry. After which the in vivo sites of phosphorylation of full-length mouse CD34 expressed from HEK293F cells were determined. The observed in vivo sites of phosphorylation, however, are not consensus PKC sites, but our data indicate that one of these sites may possibly be phosphorylated by AKT2. These results suggest that other kinases, as well as PKC, may have important signaling functions in CD34.
Related JoVE Video
Respiratory vulnerability to vehicle buffeting.
Clin. Auton. Res.
PUBLISHED: 03-29-2011
Show Abstract
Hide Abstract
Buffeting in a jerky ride in a bus or ambulance normally provokes a sustained tachypnoea driven by vibration and sensory mechanisms including vestibular signals. Tachypnoea reinforces the torso against mechanical shocks but results in overbreathing, causing a mild fall in CO(2). However, normal CO(2) is rapidly restored by a reduction in depth of breathing. We test the hypothesis that vulnerable subjects, exemplified by elderly individuals and patients with vestibular disorders, may fail to adapt to buffeting.
Related JoVE Video
Comparison of PCR ribotyping and multilocus variable-number tandem-repeat analysis (MLVA) for improved detection of Clostridium difficile.
BMC Microbiol.
PUBLISHED: 03-28-2011
Show Abstract
Hide Abstract
Polymerase chain reaction (PCR) ribotyping is one of the globally accepted techniques for defining epidemic clones of Clostridium difficile and tracing virulence-related strains. However, the ambiguous data generated by this technique makes it difficult to compare data attained from different laboratories; therefore, a portable technique that could supersede or supplement PCR ribotyping should be developed. The current study attempted to use a new multilocus variable-number tandem-repeat analysis (MLVA) panel to detect PCR-ribotype groups. In addition, various MLVA panels using different numbers of variable-number tandem-repeat (VNTR) loci were evaluated for their power to discriminate C. difficile clinical isolates.
Related JoVE Video
Preventing iatrogenic injury from inadvertent intracranial migration of a urinary foley catheter while controlling profuse epistaxis after severe craniofacial trauma.
J Craniofac Surg
PUBLISHED: 03-19-2011
Show Abstract
Hide Abstract
The massive nasopharyngeal bleeding that may accompany complicated comminuted fractures of the craniofacial bones can be controlled by pressure tamponade using an inflatable urinary Foley catheter. However, inadvertent intracranial catheter penetration poses a serious risk in such situations. Management of a relevant case is described, and a simple preventive measure is suggested.
Related JoVE Video
Adverse effects of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine in 6- to 7-year-old children.
Pediatr Neonatol
PUBLISHED: 02-17-2011
Show Abstract
Hide Abstract
Although the safety profile of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines in adolescents and adults has been documented, few data have reported about their adverse events in children. Healthy 6- to 7-year-old children who were immunized with Tdap vaccine were evaluated for adverse events on Days 1, 2, 4, and 7 postimmunization. Information of sex, body mass index (BMI), and previous diphtheria-pertussis-tetanus (DPT) immunization history was obtained and evaluated for the association with the adverse events. A total of 243 6- to 7-year-old children were immunized with Tdap. Among the 243 children immunized, remarkable adverse events included redness more than or equal to 10 mm in 47 (19%) children, induration more than or equal to 10 mm in 57 (23%), tenderness in 130 (53%), and fever in 12 (5%). Redness and induration resolved in 7 days and fever resolved on Day 4. The adverse events were not associated with gender, BMI above the mean value, or the type of fourth DPT immunization. Adverse events after Tdap vaccination were mild and dissolved within 7 days in 6- to 7-year-old children.
Related JoVE Video
A novel role for the T-box transcription factor Tbx1 as a negative regulator of tumor cell growth in mice.
Mol. Carcinog.
PUBLISHED: 02-11-2011
Show Abstract
Hide Abstract
The T-box transcription factor, Tbx1, an important regulatory gene in development, is highly expressed in hair follicle (HF) stem cells in adult mice. Because mouse models of skin carcinogenesis have demonstrated that HF stem cells are a carcinogen target population and contribute significantly to tumor development, we investigated whether Tbx1 plays a role in skin carcinogenesis. We first assessed Tbx1 expression levels in mouse skin tumors, and found down-regulation in all tumors examined. To study the effect of Tbx1 expression on growth and tumorigenic potential of carcinoma cells, we transfected mouse Tbx1 cDNA into a mouse spindle cell carcinoma cell line that did not express endogenous Tbx1. Following transfection, two cell lines expressing different levels of the Tbx1/V5 fusion protein were selected for further study. Intradermal injection of the cell lines into mice revealed that Tbx1 expression significantly suppressed tumor growth, albeit with no change in tumor morphology. In culture, ectopic Tbx1 expression resulted in decreased cell growth and reduced development into multilayered colonies, compared to control cells. Tbx1-transfectants exhibited a reduced proliferative rate compared to control cells, with fewer cells in S and G2/M phases. The Tbx1 transfectants developed significantly fewer colonies in soft agar, demonstrating loss of anchorage-independent growth. Taken together, our data show that ectopic expression of Tbx1 restored contact inhibition to the skin tumor cells, suggesting that this developmentally important transcription factor may have a novel dual role as a negative regulator of tumor growth. © 2011 Wiley Periodicals, Inc.
Related JoVE Video
Operation cancellation at Chang Gung Memorial Hospital.
Chang Gung Med J
PUBLISHED: 10-29-2010
Show Abstract
Hide Abstract
Roughly 60,000 operations are performed at our medical center every year, so making efficient use of operating rooms (OR) is an important issue. Decreasing the cancellation rate of surgery is one method that could increase efficiency. We reviewed all OR cancellations in 2007 to survey the cancellation rates and causes.
Related JoVE Video
Job stress models, depressive disorders and work performance of engineers in microelectronics industry.
Int Arch Occup Environ Health
PUBLISHED: 04-14-2010
Show Abstract
Hide Abstract
Microelectronic engineers are considered valuable human capital contributing significantly toward economic development, but they may encounter stressful work conditions in the context of a globalized industry. The study aims at identifying risk factors of depressive disorders primarily based on job stress models, the Demand-Control-Support and Effort-Reward Imbalance models, and at evaluating whether depressive disorders impair work performance in microelectronics engineers in Taiwan.
Related JoVE Video
Novel neuroprotective mechanisms of memantine: increase in neurotrophic factor release from astroglia and anti-inflammation by preventing microglial activation.
Neuropsychopharmacology
PUBLISHED: 06-17-2009
Show Abstract
Hide Abstract
Memantine shows clinically relevant efficacy in patients with Alzheimers disease and Parkinsons disease. Most in vivo and in vitro studies attribute the neuroprotective effects of memantine to the blockade of N-methyl-D-aspartate (NMDA) receptor on neurons. However, it cannot be excluded that mechanisms other than NMDA receptor blockade may contribute to the neuroprotective effects of this compound. To address this question, primary midbrain neuron-glia cultures and reconstituted cultures were used, and lipopolysaccharide (LPS), an endotoxin from bacteria, was used to produce inflammation-mediated dopaminergic (DA) neuronal death. Here, we show that memantine exerted both potent neurotrophic and neuroprotective effects on DA neurons in rat neuron-glia cultures. The neurotrophic effect of memantine was glia dependent, as memantine failed to show any positive effect on DA neurons in neuron-enriched cultures. More specifically, it seems to be that astroglia, not microglia, are the source of the memantine-elicited neurotrophic effects through the increased production of glial cell line-derived neurotrophic factor (GDNF). Mechanistic studies showed that GDNF upregulation was associated with histone hyperacetylation by inhibiting the cellular histone deacetylase activity. In addition, memantine also displays neuroprotective effects against LPS-induced DA neuronal damage through its inhibition of microglia activation showed by both OX-42 immunostaining and reduction of pro-inflammatory factor production, such as extracellular superoxide anion, intracellular reactive oxygen species, nitric oxide, prostaglandin E(2), and tumor necrosis factor-alpha. These results suggest that the neuroprotective effects of memantine shown in our cell culture studies are mediated in part through alternative novel mechanisms by reducing microglia-associated inflammation and by stimulating neurotrophic factor release from astroglia.
Related JoVE Video
Human isolates of Salmonella enterica serovar Typhimurium from Taiwan displayed significantly higher levels of antimicrobial resistance than those from Denmark.
Int. J. Food Microbiol.
Show Abstract
Hide Abstract
Salmonella enterica serovar Typhimurium is a major zoonotic pathogen with a high prevalence of antimicrobial resistance. This pathogen can disseminate across borders and spread far distances via the food trade and international travel. In this study, we compared the genotypes and antimicrobial resistance of 378 S. Typhimurium isolates collected in Taiwan and Denmark between 2009 and 2010. Genotyping revealed that many S. Typhimurium strains were concurrently circulating in Taiwan, Denmark and other countries in 2009 and 2010. When compared to the isolates collected from Denmark, the isolates from Taiwan displayed a significantly higher level of resistance to 11 of the 12 tested antimicrobials. Seven genetic clusters (A-G) were designated for the isolates. A high percentage of the isolates in genetic clusters C, F and G were multidrug-resistant. Of the isolates in cluster C, 79.2% were ASSuT-resistant, characterized by resistance to ampicillin, streptomycin, sulfamethoxazole, and tetracycline. In cluster F, 84.1% of the isolates were ACSSuT-resistant (resistant to ASSuT and chloramphenicol). Cluster G was unique to Taiwan and characterized in most isolates by the absence of three VNTRs (ST20, ST30 and STTR6) as well as a variety of multidrug resistance profiles. This cluster exhibited very high to extremely high levels of resistance to several first-line drugs, and among the seven clusters, it displayed the highest levels of resistance to cefotaxime and ceftazidime, ciprofloxacin and gentamicin. The high prevalence of antimicrobial resistance in S. Typhimurium from Taiwan highlights the necessity to strictly regulate the use of antimicrobials in the agriculture and human health care sectors.
Related JoVE Video
Fatty acid synthase overexpression confers an independent prognosticator and associates with radiation resistance in nasopharyngeal carcinoma.
Tumour Biol.
Show Abstract
Hide Abstract
Fatty acid synthase (FASN) is overexpressed in many human cancers and associated with poor prognosis. However, the role of FASN in nasopharyngeal carcinoma (NPC) has not been studied. We evaluated the expression of FASN immunohistochemically in 124 NPC specimens, stratified them into two groups (FASN-high and FASN-low), and examined the correlation with various clinicopathological parameters. In two NPC cell lines, HONE1 and TW01, we targeted the FASN transcript by shRNAi and evaluated the effect on cell proliferation by WST-1 assay and radiation-induced apoptosis by measuring caspase-3 and caspase-7 activation. NPC with high FASN immunoexpression was correlated with advanced pT disease status and worse prognosis in terms of disease-specific survival, metastasis-free survival and local recurrence-free survival, compared to FASN-low group in both univariate and multivariate analyses. In the two NPC cell lines, endogenous FASN expression was significantly higher than the non-tumor keratinocyte, DOK. When the expression of FASN was suppressed by shRNAi, the tumor cells showed decreased cell proliferation and increased apoptosis after radiation. Our results supported FASN as an adverse prognostic marker in NPC, possibly by conferring cell growth advantage and resistance to radiation-induced apoptosis on tumor cells. The inhibition of FASN expression might be investigated as an adjunct in treatment, especially in radiation resistant NPC.
Related JoVE Video
Gender difference in the prognostic role of interleukin 6 in oral squamous cell carcinoma.
PLoS ONE
Show Abstract
Hide Abstract
Interleukin 6 (IL6) plays an important role in immunoregulation and tumorigenesis in human cancers. Oral squamous cell carcinoma (OSCC) is a malignant tumor of the oral cavity with a male predominant tendency and a poor clinical prognosis. Due to the relatively few cases in females, the gender difference of prognostic markers for OSCC is seldom discussed.
Related JoVE Video
Differential impact of IL-10 expression on survival and relapse between HPV16-positive and -negative oral squamous cell carcinomas.
PLoS ONE
Show Abstract
Hide Abstract
Human papillomavirus (HPV) is a risk factor in a subset of oropharyngeal cancer; however, the contribution of HPV in the malignancy of oral squamous cell carcinomas (OSCC) is not fully understood in Taiwanese. Herein, 61 patients with no risk factors and 117 patients with one or more risk factors were enrolled in this study. HPV16/18 infection rate in non-smokers, non-drinkers and non-betel quid chewers was higher than their counterparts. The development of HPV-infected cancer has been shown to be associated with interleukin-10 (IL-10) expression. To this end, IL-10 mRNA expression in OSCC tumors was evaluated by real-time RT-PCR. Data showed that HPV-positive patients had higher IL-10 mRNA levels than in HPV-negative patients. Kaplan-Meier and Cox-regression analysis indicated that the prognostic significance of IL-10 mRNA on overall survival and relapse free survival was only observed in HPV-positive OSCC, but not in HPV-negative OSCC. Mechanistically, the elevation of IL-10 by E6 was responsible for increased colony formation and migration capability in OSCC cells. Therefore, we suggest that IL-10 induced by E6 promotes cell growth and migration capability and consequent poor survival and relapse in HPV-positive OSCC.
Related JoVE Video
Community outbreak of adenovirus, Taiwan, 2011.
Emerging Infect. Dis.
Show Abstract
Hide Abstract
In 2011, a large community outbreak of human adenovirus (HAdV) in Taiwan was detected by a nationwide surveillance system. The epidemic lasted from week 11 through week 41 of 2011 (March 14-October 16, 2011). Although HAdV-3 was the predominant strain detected (74%), an abrupt increase in the percentage of infections caused by HAdV-7 occurred, from 0.3% in 2008-2010 to 10% in 2011. Clinical information was collected for 202 inpatients infected with HAdV; 31 (15.2%) had severe infection that required intensive care, and 7 of those patients died. HAdV-7 accounted for 10%, 12%, and 41% of infections among outpatients, inpatients with nonsevere infection, and inpatients with severe infection, respectively (p<0.01). The HAdV-7 strain detected in this outbreak is identical to a strain recently reported in the Peoples Republic of China (HAdV7-HZ/SHX/CHN/2009). Absence of circulating HAdV-7 in previous years and introduction of an emerging strain are 2 factors that caused this outbreak.
Related JoVE Video
Identification of the deleted in split hand/split foot 1 protein as a novel biomarker for human cervical cancer.
Carcinogenesis
Show Abstract
Hide Abstract
The morphological detection of early neoplastic transformation leading to cervical cancer remains problematic. In this work, we have identified deleted in split hand/split foot 1 protein (DSS1) as an early biomarker that is specifically upregulated in premalignant and malignant cervical epithelial cells, but is low or undetectable in non-malignant cells. DSS1 mRNA and protein levels are significantly increased in cultured human cervical carcinoma cell lines originating from primary and metastatic tumors. In fact, > 96% of patient tumor tissues were found to have cells with elevated DSS1 when compared with tumor-adjacent normal cells. In histological sections of cervical tissue containing either invasive cervical carcinoma or its precursor lesions, DSS1 was readily detected in the tumor cells. Steady-state DSS1 expression by immortalized cervical cancer cell lines was found to be necessary for maintenance of their transformed phenotype, since stable shRNA-mediated depletion of DSS1 in HeLa cells inhibited their proliferation and colony-forming activity in monolayer cultures and prevented division of these cells in soft agar. When DSS1 levels are reduced using shRNA, the cells ultimately undergo apoptosis via activation of p53 and the p53 downstream targets, and cleavage of apoptosis-associated proteins including CPP32/caspase-3, poly(ADP-ribose)polymerase and DNA-PKcs. In addition, silencing of DSS1 makes cervical cancer cells sensitive to cell death after treatment with cisplatin. We conclude that the DSS1 protein is critically involved in the maintenance of the transformed phenotype in cervical cancer cells, and that it might be a specific, robust and reliable marker for early detection, diagnosis and treatment.
Related JoVE Video
High expression of interleukin 10 might predict poor prognosis in early stage oral squamous cell carcinoma patients.
Clin. Chim. Acta
Show Abstract
Hide Abstract
Interleukin 10 (IL10) plays an important role in immunosuppression and suppression of antitumor immunity. This study examined the IL10 expression of tumor cells and assessed its significance in patients with oral squamous cell carcinoma (OSCC).
Related JoVE Video
Inhibition of neddylation represses lipopolysaccharide-induced proinflammatory cytokine production in macrophage cells.
J. Biol. Chem.
Show Abstract
Hide Abstract
Cullin-RING E3 ligases (CRLs) are a class of ubiquitin ligases that control the proteasomal degradation of numerous target proteins, including I?B, and the activity of these CRLs are positively regulated by conjugation of a Nedd8 polypeptide onto Cullin proteins in a process called neddylation. CRL-mediated degradation of I?B, which normally interacts with and retains NF-?B in the cytoplasm, permits nuclear translocation and transactivation of the NF-?B transcription factor. Neddylation occurs through a multistep enzymatic process involving Nedd8 activating enzymes, and recent studies have shown that the pharmacological agent, MLN4924, can potently inhibit Nedd8 activating enzymes, thereby preventing neddylation of Cullin proteins and preventing the degradation of CRL target proteins. In macrophages, regulation of NF-?B signaling functions as a primary pathway by which infectious agents such as lipopolysaccharides (LPSs) cause the up-regulation of proinflammatory cytokines. Here we have analyzed the effects of MLN4924, and compared the effects of MLN4924 with a known anti-inflammatory agent (dexamethasone), on certain proinflammatory cytokines (TNF-? and IL-6) and the NF-?B signaling pathway in LPS-stimulated macrophages. We also used siRNA to block neddylation to assess the role of this molecular process during LPS-induced cytokine responsiveness. Our results demonstrate that blocking neddylation, either pharmacologically or using siRNA, abrogates the increase in certain proinflammatory cytokines secreted from macrophages in response to LPS. In addition, we have shown that MLN4924 and dexamethasone inhibit LPS-induced cytokine up-regulation at the transcriptional level, albeit through different molecular mechanisms. Thus, neddylation represents a novel molecular process in macrophages that can be targeted to prevent and/or treat the LPS-induced up-regulation of proinflammatory cytokines and the disease processes associated with their up-regulation.
Related JoVE Video
Human papilloma virus 16 E6 oncoprotein associated with p53 inactivation in colorectal cancer.
World J. Gastroenterol.
Show Abstract
Hide Abstract
To investigate the association between human papilloma virus (HPV) infection and colorectal cancer.
Related JoVE Video
Interleukin-10 haplotype may predict survival and relapse in resected non-small cell lung cancer.
PLoS ONE
Show Abstract
Hide Abstract
IL-10 is associated with tumor malignancy via immune escape. We hypothesized that IL-10 haplotypes categorized by IL-10 promoter polymorphisms at -1082A>G, -819C>T, and -592C>A might influence IL-10 expression and give rise to non-small cell lung cancer (NSCLC) patients with poor outcomes and relapse. We collected adjacent normal tissues from 385 NSCLC patients to determine IL-10 haplotypes by direct sequencing and polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Of the 385 tumors, 241 were available to evaluate IL-10 mRNA expression levels by real-time RT-PCR. The influence of IL-10 haplotypes on overall survival (OS) and relapse free survival (RFS) were determined by Kaplan-Meier and multivariate Cox regression analysis. The results showed that IL-10 mRNA levels were significantly higher in tumors with the non-ATA haplotype than with the ATA haplotype (P?=?0.004). Patients with the non-ATA haplotype had shorter OS and RFS periods than did patients with the ATA haplotype. This may be associated with the observation that the number of tumor-infiltrating lymphocytes was decreased in the tumors with higher levels of IL-10. Consistently, T cells from the peripheral blood of the patients with non-ATA haplotype were more susceptible to apoptosis and less cytotoxic to tumor cells, compared to those from the patients with ATA haplotype. The results suggest that IL-10 can promote tumor malignancy via promoting T cell apoptosis and tumor cell survival, and IL-10 haplotype evaluated by PCR-RFLP or direct sequencing may be used to predict survival and relapse in resected NSCLC, helping clinicians to make appropriate decisions on treatment of the patients.
Related JoVE Video
Expression of cyclin-dependent kinase 2-associated protein 1 confers an independent prognosticator in nasopharyngeal carcinoma: a cohort study.
J. Clin. Pathol.
Show Abstract
Hide Abstract
Low expression of cyclin-dependent kinase 2-associated protein (CDK2AP1) is associated with tumour progression in oral and oesophageal carcinomas, but is not well studied in patients with head and neck cancer and nasopharyngeal carcinoma (NPC).
Related JoVE Video
Diaphoresis and abdominal pain caused by extra-adrenal paragangliomas.
BMJ Case Rep
Show Abstract
Hide Abstract
A 63-year-old lady presented with suprapelvic pain, weight loss and night sweats. On examination, she was noted to be hypertensive with a distended abdomen. Imaging (CT) revealed a 9.5 cm retroperitoneal mass with a high degree of vascularity and necrotic centre. The patients urinary and plasma catecholamines were significantly raised and subsequent radio-isotope scan suggested the tumour was likely to be of a neuroendocrine nature. A diagnosis of a malignant paraganglioma was made. Malignant paragangliomas derive from sympathetic tissue and secrete catecholamines. Diagnostic uncertainty might lead to biopsy of tumour but this carries a high-risk of catecholamine-induced complications such as hypertensive crisis, cardiac arrhythmias and cardiac ischaemia and must be avoided.
Related JoVE Video
Rsf-1 expression in rectal cancer: with special emphasis on the independent prognostic value after neoadjuvant chemoradiation.
J. Clin. Pathol.
Show Abstract
Hide Abstract
Neoadjuvant chemoradiation therapy (CRT) is an increasingly used therapeutic strategy for rectal cancer. Clinically, it remains a major challenge to predict therapeutic response and patient outcome after CRT. Rsf-1 (HBXAP), a novel nuclear protein with histone chaperon function, mediates ATPase-dependent chromatin remodelling and confers tumour aggressiveness and predicts therapeutic response in certain carcinomas. However, the expression of Rsf-1 has never been reported in rectal cancer. This study examined the predictive and prognostic impacts of Rsf-1 expression in patients with rectal cancer following neoadjuvant CRT.
Related JoVE Video
Loss of epithelial membrane protein-2 expression confers an independent prognosticator in nasopharyngeal carcinoma: a cohort study.
BMJ Open
Show Abstract
Hide Abstract
To evaluate the expression of epithelial membrane protein-2 (EMP2) protein and its clinicopathological associations in patients with nasopharyngeal carcinoma.
Related JoVE Video
simple hit counter

What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

How does it work?

We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.